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John G. Frelinger, Ph.D.

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Research Labs

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Locations

University of Rochester Medical Center
School of Medicine and Dentistry
601 Elmwood Ave, Box 704
Rochester, NY 14642

Faculty Appointments

Biography

Research

My laboratory has a number of interests united by the common theme of T cell recognition. One focus of research has been the generation and maintenance of effective T cell responses to tumors. It has become apparent that anti-tumor responses can be directed against differentiation antigens. Thus, even with multiple mechanisms of establishing and maintaining tolerance, tolerance is not absolute. We hypothesize that it is possible to direct an effective response against tumors by inducing an autoimmune response to organ-specific antigens. To examine this hypothesis, we will use transgenic mice lines we have developed which specifically express human PSA in the prostate and investigate how this expression affects their ability to generate CTL responses to human PSA using novel immunization strategies. In this light, we have been working on developing novel viral vectors for immunization. Helper free herpes amplicons, plasmid based vectors that have an extremely large coding capacity, are attractive viral vaccine candidates for expressing recombinant proteins in vivo for immunization. The amplicon system has particular promise since it encodes no viral gene products and we have shown it very effectively infects dendritic cells. In collaboration with Edith Lord and in conjunction with Tom Foster's laboratory in the Department of Imaging Sciences, we have devised imaging approaches to look at the early steps in immunization and at the effector T cells generated. These studies will contribute to the rational design of immunotherapy for tumors as well as for HIV. We also believe that many of the techniques and approaches will be applicable to other infectious agents as well. In this regard, we are collaborating with investigators at University of North Carolina to identify T cell epitopes of Francisella tularensis. Francisella tularensis (FT) is a gram negative bacterium that is able to infect a wide range of mammalian hosts. FT has several properties that suggest could be developed as a biological weapon, including its ability to be aerosolized and its low LD50. Indeed, it has been asserted that FT was used as a bioweapon in World War II. Unfortunately relatively little information is available concerning the detailed cellular mechanism of resistance to re-infection either in humans or in experimental animals. However, as expected for a pathogen that grows largely intracellularly, T cells are believed to be a critical component in resistance to reinfection and recovery from primary infection. My laboratory has developed a technique called the TCAD ( the T-Cell antigen discovery technique) to identify and improve T cell epitopes, originally in the context of tumor vaccines. We have recently modified this system to large-scale screens for the identification of T cell epitopes from FT using this system which takes advantage of the tremendously enhanced efficiency particulate antigen cross-priming and a novel reporter system of T cell activation. It is hoped that the identification of the T cell epitopes recognized will yield to a batter understanding of the nature of a protective response and ultimately a defined vaccine.

Credentials

Education

1975
BS with Distinction and Departmental Honors | Stanford University
Biology

1980
PhD | California Institute of Technology
Biochemistry

Post-doctoral Training & Residency

1983 - 1984
Senior Postdoctoral Fellow, American Cancer Society, California Division, Stanford University. Mentor: Dr. C.G. Fathman, Immunology

1981 - 1983
Jane Coffin Childs Fellow, Immunology, Stanford University, Mentor: Dr. C.G. Fathman, Immunology

1980 - 1981
NIH Postdoctoral Fellow, Caltech, Pasadena, CA. Mentor: Dr. Leroy Hood, Molecular Biology

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Awards

2016
Manuel D. Goldman Prize for Excellence in Teaching Medical School

2015
Special Commendation for Teaching-Medical School

2014
Chair Education Committee (AAI)
Sponsor: AAI

2012
Alumni Gold Medal Teaching Award

2011 - 2014
AAI Education Committee
Sponsor: American Association of Immunologists

2002
Special Commendation Teaching-Medical School

2000
Distinguished Speaker
Location: University of Texas at San Antonio

2000
Faculty Speaker, Medical School Class of 2000 Awards Ceremony

1998
Herbert W. Mapstone Prize for Teaching Excellence

1996
Special Commendation Teaching-Medical School

1995
Herbert W. Mapstone Prize for Teaching Excellence

1994
Special Commendation Teaching-Medical School

1991 - 1993
Andrew W. Mellon Deans Teaching Scholar
Sponsor: Excellence in Teaching and Research

1986 - 1988
Junior Faculty Research Award
Sponsor: American Cancer Society

1983 - 1984
American Cancer Society Senior Fellowship, California Division

1981 - 1983
Jane Coffin Childs Fellowship

1975
B.S. with Distinction and Departmental Honors

1971 - 1975
National Merit Scholarship

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Patents

Patent Title: Protease Activated Cytokines
Patent #: 8,734,774
Issue Date: May 27, 2014
Country: United States
Invented By: John G Frelinger, Baek Kim, John Puskas, Mark A Sullivan

Patent Title: Prostate Specific Regulatory Nucleic Acid Sequences and Transgenic Non-Human Animals Expressing Prostate Specific Antigen
Patent #: 6,100,444
Issue Date: Aug 08, 2000
Country: United States
Invented By: Richard K Barth, John G Frelinger, Chungwen Wei

Patent Title: Helper Virus-Free Herpesvirus Amplicon Particles and Uses Thereof
Patent #: DE1346036
Issue Date: Apr 28, 2010
Country: Germany
Invented By: William J Bowers, Stephen Dewhurst, Thomas G Evans, Howard J Federoff, John G Frelinger, Peter K Hocknell, Joseph D Rosenblatt, Khaled A Tolba, Richard A Willis

Patent Title: Helper Virus-Free Herpesvirus Amplicon Particles and Uses Thereof
Patent #: FR1346036
Issue Date: Apr 28, 2010
Country: France
Invented By: William J Bowers, Stephen Dewhurst, Thomas G Evans, Howard J Federoff, John G Frelinger, Peter K Hocknell, Joseph D Rosenblatt, Khaled A Tolba, Richard A Willis

Patent Title: Helper Virus-Free Herpes Virus Amplicon Particles and Uses Thereof
Patent #: 8,119,118
Issue Date: Feb 21, 2012
Country: United States
Invented By: William J Bowers, Stephen Dewhurst, Thomas G Evans, Howard J Federoff, John G Frelinger, Joseph D Rosenblatt, Khaled A Tolba, Richard A Willis

Patent Title: Helper Virus-Free Herpes Virus Amplicon Particles and Uses Thereof
Patent #: 1346036
Issue Date: Apr 28, 2010
Country: Europe
Invented By: William J Bowers, Stephen Dewhurst, Thomas G Evans, Howard J Federoff, John G Frelinger, Peter K Hocknell, Joseph D Rosenblatt, Khaled A Tolba, Richard A Willis

Patent Title: Helper Virus-Free Herpes Virus Amplicon Particles and Uses Thereof
Patent #: IE1346036
Issue Date: Apr 28, 2010
Country: Ireland
Invented By: William J Bowers, Stephen Dewhurst, Thomas G Evans, Howard J Federoff, John G Frelinger, Peter K Hocknell, Joseph D Rosenblatt, Khaled A Tolba, Richard A Willis

Patent Title: Helper Virus-Free Herpes Virus Amplicon Particles and Uses Thereof
Patent #: GB1346036
Issue Date: Apr 28, 2010
Country: United Kingdom
Invented By: William J Bowers, Stephen Dewhurst, Thomas G Evans, Howard J Federoff, John G Frelinger, Peter K Hocknell, Joseph D Rosenblatt, Khaled A Tolba, Richard A Willis

Patent Title: Helper Virus-Free Herpes Virus Amplicon Particles and Uses Thereof
Patent #: DK1346036
Issue Date: Apr 28, 2010
Country: Denmark
Invented By: William J Bowers, Stephen Dewhurst, Thomas G Evans, Howard J Federoff, John G Frelinger, Peter K Hocknell, Joseph D Rosenblatt, Khaled A Tolba, Richard A Willis

Patent Title: Helper Virus-Free Herpes Virus Amplicon Particles and Uses Thereof
Patent #: BE1346036
Issue Date: Apr 28, 2010
Country: Belgium
Invented By: William J Bowers, Stephen Dewhurst, Thomas G Evans, Howard J Federoff, John G Frelinger, Peter K Hocknell, Joseph D Rosenblatt, Khaled A Tolba, Richard A Willis

Patent Title: Helper Virus-Free Herpes Virus Amplicon Particles and Uses Thereof
Patent #: 2002246625
Issue Date: Apr 24, 2008
Country: Australia
Invented By: William J Bowers, Stephen Dewhurst, Thomas G Evans, Howard J Federoff, John G Frelinger, Peter K Hocknell, Joseph D Rosenblatt, Khaled A Tolba, Richard A Willis

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Publications

Journal Articles

5/2016
Mikucki ME, Skitzki JJ, Frelinger JG, Odunsi K, Gajewski TF, Luster AD, Evans SS. "Unlocking tumor vascular barriers with CXCR3: Implications for cancer immunotherapy." Oncoimmunology.. 2016 May 0; 5(5):e1116675. Epub 2016 Feb 11.

9/2015
Skrombolas D, Wylie I, Maharaj S, Frelinger JG. "Characterization of an IL-12 p40/p35 Truncated Fusion Protein That can Inhibit the Action of IL-12." Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research.. 2015 Sep 0; 35(9):690-7. Epub 2015 May 04.

6/25/2015
Mikucki ME, Fisher DT, Matsuzaki J, Skitzki JJ, Gaulin NB, Muhitch JB, Ku AW, Frelinger JG, Odunsi K, Gajewski TF, Luster AD, Evans SS. "Non-redundant requirement for CXCR3 signalling during tumoricidal T-cell trafficking across tumour vascular checkpoints." Nature communications.. 2015 Jun 25; 6:7458. Epub 2015 Jun 25.

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